rs10778724

chr12-80318152-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378609.3(OTOGL):c.3635-394C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,072 control chromosomes in the GnomAD database, including 61,900 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61900 hom., cov: 31)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3	c.3635-394C>T		intron_variant		ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7	c.3635-394C>T		intron_variant		5	NM_001378609.3	P1
OTOGL	ENST00000646859.1	c.3500-394C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136024 AN: 151954 Hom.: 61874 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.926

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.895 AC: 136108 AN: 152072 Hom.: 61900 Cov.: 31 AF XY: 0.895 AC XY: 66576 AN XY: 74354

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.926

Alfa AF: 0.957 Hom.: 29754

Bravo AF: 0.880

Asia WGS AF: 0.923 AC: 3213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.2
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10778724; hg19: chr12-80711932;